Increased Thyroxine Clearance in Rats Treated with High Doses of a Histamine H2-Antagonist, SKF 93479
Treatment of rats with high doses (200-1000 mg/kg) of a histamine H2-antagonist, SKF 93479 (2-(2-(5-(dimethylaminomethyl)furan-2-ylmethylthio)-furan-2-ylmethyl-amino)-5-(6-methylpyrid-3-ylmethyl)pyrimidin-4-one trihydrochloride), is associated with histological changes in the thyroid glands. These changes were observed as early as 3 days after the start of treatment, and include follicular cell hypertrophy and colloid depletion, which are indicative of increased thyroid activity. Similar thyroid histological changes have previously been observed in rats following treatment with classical antithyroid compounds such as methimazole (Owen et al. 1973). Several investigations were carried out in order to determine the mechanism of the effect of SKF 93479 on thyroid activity. In particular, the possibility of a direct or indirect effect of the compound (the latter via alterations in the pituitary feedback mechanism) was examined by studying plasma thyroxine (T4) and thyroid stimulating hormone (TSH) concentrations, thyroidal iodide-125 uptake and T4 clearance in rats treated with SKF 93479.
KeywordsToxicity Ethyl Iodide Histamine Diphenylhydantoin
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